Epstein-Barr virus (EBV) is associated with a wide spectrum of benign and malignant diseases. Recent additions to the list include oral hairy leukoplakia; a subset of Hodgkin's lymphomas, particularly those with mixed cellularity histology or those occurring in underdeveloped countries; a subset of diffuse large cell/immunoblastic lymphoma in the immunocompromised, particularly primary central nervous system lymphoma; a subset of peripheral T cell lymphomas; and a subset of gastric carcinomas, particularly undifferentiated carcinomas. There are several distinctive aspects of the biology of the virus that are important in investigations of virus in clinical specimens. The presence of repeated elements in the genome facilitates detection of viral nucleic acids by a variety of hybridization techniques as well as the characterization of the clonality of virus-infected tissues. Latent viral infection is associated with several different patterns of viral gene expression in infected cells. Latent gene products are important because of their growth-regulating and -transforming properties as well as the potent cytotoxic T cell response they elicit. The abundant expression of the EBER RNA transcripts makes possible the sensitive detection of latent infection in EBV-associated tumors. Lytic infection can be inhibited by antiviral nucleoside analogues. Two lytic gene products are of special interest because of their homology to the cellular proteins BCL-2 and interleukin-10. Two viral biotypes or strains with different properties in terms of lymphocyte immortalization and transformation have recently been characterized. Current evidence suggests a differential biotype association with particular malignancies. Characterization of the association of EBV with various disease processes promises to be important for diagnosis and treatment as well as for a better understanding of the epidemiology and pathogenesis of these diabetes.